The Cold Spring Harbor Laboratory proposes to continue a course entitled Computational and Comparative Genomics, to be held in the fall of 2014 - 2016. The Computational and Comparative Genomics course provides experimental biologists with backgrounds in molecular biology, genetics, and biochemistry with the theoretical background and practical experience necessary to use and evaluate computational approaches to genome annotation and analysis, including protein sequence database searching, multiple sequence alignment, identification of promoters and other genetic regulatory elements, and the integration of sequence information into broader models of biological function. The course also provides computer scientists and mathematicians with an introduction to the algorithms, computational methods, and biological problems that are addressed in biological sequence analysis and computational biology. For post-doctoral fellows, and junior and senior investigators who are interested in changing their research direction towards computational biology, the course provides an introduction to computational biology methods and a survey of future directions. Over a seven day period, the students receive a strong grounding in the both the biological and computer science foundations for genome analysis and practical computer laboratory experience on challenging problems. The course is taught by internationally recognized leaders in the field, who provide hands-on demonstrations of the programs and biological databases they have developed. At the end of the course, students can not only use effectively currently available tools in biological sequence analysis, they can also evaluate critically new computational approaches by considering alternative methods and interpretations, and appreciate the strengths and limitations of computational methods for answering broad biological questions.